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Once-Fatal Metabolic Disorders Treatable, Says Stanford/Packard,Researcher

amage, coma and death.

If a diagnosis is made quickly enough, dialysis can help to cleanse the blood of excess nitrogen during an episode and prevent brain damage.

Traditional treatments included maintaining a very-low protein diet that is still high enough in calories to avoid metabolizing any of the body's protein-rich muscle. Liver transplantation is also an option for some patients.

This study investigated whether drugs that promote alternative pathways to dismantle and excrete nitrogen-containing waste can lower the dangerously high levels of blood ammonia, called hyperammonemia.

The 299 people in the study experienced 1,181 episodes of hyperammonemia during the study period. Those who received the drug therapy had an overall survival rate of 73 percent for newborns and 98 percent for older patients. In contrast, a recent European study of 217 patients who did not receive the therapy reported overall survival rates of only 16 percent for newborns and 72 percent for people with later onset of disease.

Urea cycle disorders can become apparent at many different stages in life. Newborns with a complete blockage in the cycle begin to show symptoms within hours after birth but are often misdiagnosed. Older children or adults with less-severe mutations can lead normal lives until sickness or a change in diet overtax the body and bring on a life-threatening episode.

Only a fraction of the many possible mutations are picked up by expanded newborn screening, and precious days are lost while test results are processed. The lethargy, vomiting and rapid breathing exhibited by affected newborns are often misinterpreted and mistreated as hospital-acquired infections. "Newborn screening is good at detecting some urea cycle disorders, but we can't diagnose all of them this way," said Enns. "By the time the results come back, these kids are already in the hospital and going into a coma. The sooner you identify them, the better the possib
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